In preliminary work we have demonstrated that alpha-haloalkyl ketoximes can function as selective alkylating agents in biological systems. The current phase of our research has four principal facets. 1) We will continue to delineate reactivity patterns in the alkylation of protein functional groups with aryl alpha-haloalkyl ketoximes and related derivatives. These patterns will be helpful in developing the use of the ketoximes as selective biological alkylating agents. 2) It has been suggested that the mode of action of tumor inhibitors like taxodone and vernolepin may involve the selective alkylation of certain protein sulfhydryl groups. Thus, we plan to ask NCI to test the antitumor activity of alpha-haloalkyl ketoxime derivatives which show marked selectivity in the alkylation of sulfhydryl groups in enzymes. 3) While we have obtained kinetic evidence for the intermediacy of alpha-nitrosostyrene in those nucleophilic reactions of alpha-haloacetophenone oximes proceeding through an elimination-addition route, direct detection of such intermediates remains an objective for future research. Also, the possibility that species like alpha-nitrosostyrene formed by elimination from alpha-haloalkyl ketoximes can be trapped in cycloaddition reactions will be investigated from both the mechanistic and synthetic standpoints. 4) Finally, the potential application of the chemistry of alpha-haloalkyl ketoximes in facilitating peptide synthesis by the solid phase method will be explored.